DEFINITION update and REMOVE PARENT retrograde protein transport, ER to cytosol (GO:0030970)

[ValWood]

retrograde protein transport, ER to cytosol (GO:0030970) is defined The directed movement of unfolded or misfolded proteins from the endoplasmic reticulum to the cytosol through the translocon. [PMID:11994744]

but is not a descendant of

ubiquitin-dependent ERAD pathway (GO:0030433) The series of steps necessary to target endoplasmic reticulum (ER)-resident proteins for degradation by the cytoplasmic proteasome. Begins with recognition of the ER-resident protein, includes retrotranslocation (dislocation) of the protein from the ER to the cytosol, protein ubiquitination necessary for correct substrate transfer, transport of the protein to the proteasome, and ends with degradation of the protein by the cytoplasmic proteasome. [PMID:14607247, PMID:19520858]

it seems that it should be?

[pgaudet]

GO:0030970 sounds more general than GO:0030433, but maybe there is a mistake in the definiton of GO:0030970 - the transport is via the retrotranslocon, not the translocon (see also https://en.wikipedia.org/wiki/Translocon)

But in this case - are those 2 terms really different ?

[ValWood]

Probably the same, see: https://github.com/geneontology/go-ontology/issues/20914

[ValWood]

There are papers that suggest the involvement of the translocon https://europepmc.org/article/MED/10635318 (Old) but newer papers do not mention the translocon https://europepmc.org/article/MED/24807418

Suggest i) revise def to The retrotranslocation of unfolded, misfolded or damaged proteins from the endoplasmic reticulum to the cytosol.

ii) remove parent "protein exit from the ER". The ER exit site is the site where new COPII? vesicles form, and this exit site/process is completely different (related to vesicle-mediated transport, not ERD)

ii) The ERAD paernt is OK< as this will be the one retained after the merges

[pgaudet]

Hi @ValWood I am not sure retrograde transport always leads to degradation, see

• https://pubmed.ncbi.nlm.nih.gov/36933283: movement of incorrectly localized proteins & recycling
• https://pubmed.ncbi.nlm.nih.gov/36895788: recycling of proteins
• https://pubmed.ncbi.nlm.nih.gov/34012437: silencing STING signaling pathway

So, I dont think this parent would be right.

That being said, when I look for 'retrograde transport', it seems like this refers to 'Golgi-to-ER', not ER to cytosol. I seems like 'retrotranslocation' and 'retrograde transport' mean different things? ie GO:0030970 term label is wrong WRT its definition?

[ValWood]

Yes I think something got mixed up over time. The term more closely matches the exact synonym

protein retrotranslocation, ER to cytosol | exact

I don't think this is usually called retrograde transport. That seems to be https://www.ebi.ac.uk/QuickGO/term/GO:0006890 retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (i.e vesicle mediated)

This term seems to be a slight conflation, I'm not sure that it is necessary, maybe obsoletion is better recommending either

ERAD (ER to cytosol for degradation) the ubiquitin mediated extraction, and degradation

or retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum for vesicle mediate d recycling.

The term was definitely intended for the ERAD pathway translocation

[pgaudet]

The term was definitely intended for the ERAD pathway translocation

But the reference cited for the term (in the def xref) talks about retrotranslocation, not retrograde transport...

We need to look at annotations to know how people used these terms- there are 'only' 60 annotations, see https://github.com/geneontology/go-annotation/issues/4826

[ValWood]

Yes, I think the term was intended for retrotranslocation but he use of retrograde in the name might have confused the usage. If all of the usage conforms to ERAD, it's fine to swap the names

[pgaudet]

and make sure references are appropriate